1. Field of the Invention
The present invention is directed to tyrosine kinase with Ig and EGF homology domains (“TIE”)-2 ligands, as well as to methods of making and using the TIE-2 ligands.
2. Description of Related Art
A gene encoding an endothelial cell transmembrane tyrosine kinase, originally identified by RT-PCR as an unknown tyrosine kinase-homologous cDNA fragment from human leukemia cells, was described by Partanen et al. (1990) Proc. Natl. Acad. Sci. USA, 87: 8913-8917. This gene and its encoded protein are called “TIE” which is an abbreviation for “tyrosine kinase with Ig and EGF homology domains.” Partanen et al. (1992) Mol. Cell. Biol. 12: 1698-1707.
Two structurally related rat TIE receptor proteins have been reported to be encoded by distinct genes with related profiles of expression. One gene, termed tie-1, is the rat homolog of human tie. Maisonpierre et al. (1993) Oncogene 8: 1631-1637. The other gene, tie-2, may be the rat homolog of the murine tek gene, which, like tie, has been reported to be expressed in the mouse exclusively in endothelial cells and their presumptive progenitors. Dumont, et al. Oncogene 8: 1293-1301 (1993). The human homolog of tie-2 is described in U.S. Pat. No. 5,447,860.